High intensity interval exercise increases the frequency of peripheral PD-1+ CD8+ central memory T-cells and soluble PD-L1 in humans

Exercise can exert anti-inflammatory effects in an intensity-dependent manner; however, the mechanisms mediating these effects are continually being established. Programme Death Receptor-1 (PD-1) is a membrane bound receptor that maintains immune tolerance by dampening immune cell interactions, such as those mediated by cytotoxic T-cell lymphocytes (CD8+). The aim of this study was to characterise sub-populations of CD8+ T-cells with regards to their expression of PD-1 before and immediately after exercise. Interleukin (IL)-6, soluble PD-1 (sPD-1) and its ligand (sPD-L1) were also quantified in plasma. Eight individuals (mean ± SD: age 29 ± 5 years; BMI 24.2 ± 3.4 kg.m2; O2max 44.5 ± 6.4 ml·kg-1·min-1) undertook two time and energy-matched cycling bouts in a counterbalanced study design: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE). Both MOD and HIIE increased the number, but not the proportion of circulating CD8+ PD-1+ cells, with no differences between trials. Within the CD8+ PD-1+ pool, the expression of PD-1 increased on central memory cells following HIIE only (fold change: MOD 1.0 vs HIIE +1.4), as well the concentration of CD8+PD-1+ memory cells within the circulation (cells/uL: MOD -0.4 vs HIIE +5.8). This response composed a very small part of the exercise-induced CD8+ lymphocytosis (Pre-Ex: 0.38% to Post-Ex: 0.69%; p>.05). sPD-L1 and IL-6 concentration increased in tandem following MOD and HIIE (r=0.57; P=0.021), with a reciprocal decline in sPD-1 observed. The current data demonstrate that PD-1+ CD8+ lymphocytes were mobilised following both MOD and HIIE. Both the number of central memory CD8+ T-cells expressing PD-1 and the expression level on these cells were increased following HIIE only. This intensity-dependent phenotypic response, in conjunction with increased circulatory sPD-L1 may represent an aspect of the anti-inflammatory response to exercise and warrants further investigation.